EP3466419A1 - Use of trimethoxybenzyl acetylsinapate, advantageously in combination with at least one sunscreen, for protecting the skin - Google Patents

Abstract

The present invention relates to the use of trimethoxybenzyl acetylsinapate, advantageously in combination with at least one sunscreen, for the protection of the skin.

Description

Field of the invention

The present invention relates in particular to cosmetic or dermatological compositions intended for the protection of skin cells and / or integuments against solar radiation, in particular ultraviolet radiation.

State of the art

The sun emits several categories of radiation some of which penetrates the atmosphere, including ultraviolet (100 to 400 nm), visible light (400 and 700 nm) and infrared light (700 nm to 1 mm).

The sun has certain beneficial effects in humans, such as its antirachitic or antidepressant action. Light-emitting radiations, especially UV-A and UV-B type A and B, are necessary for the good functioning of the human body, but they also have deleterious effects (photodermatoses and photo-carcinogenesis). especially).

Ultraviolet (UV) radiation itself consists of light with a wavelength between 100 nm and 400 nm, traditionally divided into 3 subgroups: UV-A (400-315 nm), UV-B ( 315-280 nm) and UV-C (280-100 nm). Short-wave UV-C is the most energetic and harmful UV, but is filtered by the ozone layer of the atmosphere and does not reach the Earth's surface. However, due to the depletion of the ozone layer in some regions of the globe, sunlight reaching the Earth's surface tends to become richer in UV radiation, especially UV-C (Lloyd et al. 1993). Most damage to the skin is still caused by UV-A and UV-B.

UV-B is more particularly at the origin of the stimulation of the production of the natural pigment of the skin called melanin, this phenomenon being commonly called tanning. UV-B also stimulates skin cells to produce a thicker epidermis. These reactions are a defense mechanism of the body against UV rays. UV-B is more energetic than UV-A and is responsible for solar erythema (or "sunburn"), which exhibits its maximum inflammatory intensity 24 hours after exposure.

The important energy of UV-B also causes molecular disorders, such as DNA damage and protein damage (including carbonylation). In the long term, these degradations saturate and block the nuclear DNA repair system. This leads to permanent mutations in the genome of affected cells, inducing the appearance of skin cancers. This is referred to as direct UV-B toxicity.

UV-A, which does not show visible harmful effects in the short term, have long been considered harmless. However, it is now widely recognized that UV-A penetrates the deep layers of the skin, and has an effect on connective tissue and blood vessels. These rays are particularly at the origin of the phenomenon called heliodermia, that is to say the premature actinic aging of the skin.

In addition, although UV-B is the main cause of cutaneous cancers, UV-A also have an indirect contribution to this type of damage. Indeed, the UV-A are at the origin of the production of free radicals, in particular the ROS (" Reactive Oxygen Species " or reactive oxygen species (ROS)). These molecules are very unstable and have a very short half-life, ranging from nanoseconds to milliseconds. ROS are able to damage both cellular structures (DNA, membranes, intracellular proteins) and extracellular structures (components of the extracellular matrix such as collagen fibers). ROS also exert an indirect harmful action, causing the oxidation of membrane lipids, which induces the formation of carbonyl reactive species, helping to amplify the tissue and cell damage caused. The same damage is also caused or amplified by environmental pollution, which also generates free radicals responsible for skin aging.

A permanent concern is therefore to combat the harmful effects of UV radiation, in particular UV-A and UV-B, taking into account the type of skin (phototype) and the exposure time to the sun.

There are two ways to minimize sun damage to the skin: external protection and internal protection.

External protection is achieved by filtering the UV radiation that penetrates the skin or obscuring the areas exposed to the sun. Although covering the exposed areas provides the best photoprotection, it is not always possible or practical. For this reason, solar compositions are necessary to ensure a photoprotection of the areas exposed to UV radiation. These compositions are generally in the form of lotion, oil, emulsion of oil-in-water (O / W) or water-in-oil (W / O) type, foam, gel, stick or spray. They contain, in a cosmetically acceptable carrier and at various concentrations, one or more chemical or mineral filters.

Chemical filters are organic compounds that absorb light by creating a filter layer on the skin that neutralizes UV rays. Thus, when the solar filter molecule receives UV radiation, it goes into an excited state by absorbing the energy of the radiation and then returns to its stable state. By this mechanism, the luminous radiation is converted into heat and thus dissipated. Thus, chemical filters act in the same way as melanin, the natural photoprotective pigment of the skin, whose synthesis is stimulated by UV-B.

The filter associations, which have different absorption spectra, and the quantities used, are selected. This selection is based on the level of sun protection sought and the area of the body to be protected, taking into account the degree of vulnerability due to the thickness of the skin.

Over the last decades, increasingly efficient chemical filters have been developed, with increased photostability and broad absorption spectra for UV-A and / or UV-B. These chemical filters provide good photoprotection but their massive use is increasingly criticized. Indeed, they often have allergenic properties and can be toxic or harmful if they penetrate through the epidermal barrier. Thus, several filters are suspected to be endocrine disruptors. In addition, filters are often poorly biodegradable and become environmental pollutants. Among other examples of ecotoxic effects, sunscreens have a negative impact on marine reefs and are particularly responsible for the phenomenon of coral bleaching (Danovaro et al., 2008).

Mineral filters or physical screens are, in turn, inert and opaque powders that reflect light. Examples of well known mineral filters are zinc oxide, iron oxide, titanium dioxide and cerium oxide. Mineral filters act as mirrors and reflect solar radiation. The advantage of these filters is that they do not penetrate the skin, are hypoallergenic, and generally less ecotoxic.

However, the compositions containing high doses of mineral filters leave white marks on the skin, spread out with difficulty and can dry out the skin. These problems have now been solved by reducing the mineral filters to the state of nanoparticles. But, the recoil is not yet enough to be able to affirm with certainty that the mineral screens in the form of nanoparticles have no detrimental consequences on the human organism. The general trend is therefore to limit, as far as possible, the use of chemical or mineral filters in solar products.

An alternative or supplement to external sun protection is the internal sun protection, which consists in strengthening the skin's defenses by acting on the endogenous mechanisms that regulate the natural response of cells to solar radiation.

To fight against photo-oxidative stress and UV-induced damage, cells have complex defense systems. These mechanisms are present in all the cells of the organism and are more particularly developed at the level of the cells of the skin, because of its exposure to UV.

Internal protection is based on the observation that these endogenous cellular defenses can be induced, in order to improve the effectiveness of the cutaneous response to damage and mutations caused by solar radiation and / or environmental pollutants.

A key mediator of the antioxidant response of the skin is the protein of the bZIP family, Nrf2 ("Nuclear factor erythroid-2-related factor 2 "). The Nrf2 protein, also known as NFE2L2, is a transcription factor that controls the expression of several antioxidant genes in cells. In the physiological state, the Nrf2 protein is bound to the protein Keap-1 ("Kelch-like ECH-associated protein 1 "), forming a cytoplasmic complex inhibiting the action of Nrf2. In response to oxidative stress and in the presence of the inducers of the antioxidant response, Keap-1 is inactivated allowing Nrf2 release: The active Nrf2 transcription factor is translocated into the nucleus where it attaches to a class of promoters specific for gene expression, the ARE (" Antioxidant Response Element "). It induces the transcription of many genes involved in the response to oxidative stress and cellular detoxification.

At the skin cell level, Nrf2 is described for its central role in the UV-induced damage protection process by activating the expression of many genes involved in ROS detoxification. In addition, Nrf2 protein stimulates the production of phase II detoxification enzymes involved in the synthesis of antioxidants (including glutathione, NADPH and thioredoxin) and conjugation to graft molecular radicals to promote elimination. of these metabolites (Gorrini et al., 2013).

In practice, the function of the Nrf2 protein has been demonstrated by examining the genotype of a mouse line for which the expression of the Nrf2 gene is suppressed ( Knockout Mouse (KO) nrf-2- / -). Thus, KO Nrf2 mice show a reduction in the expression level, basal and induced, cytoprotective genes and are more vulnerable to the toxicity induced by the ROS (Copple et al., 2008). In addition, Nrf2 KO mice show a higher rate of cellular apoptosis and oxidative damage in keratinocytes after UV-B irradiation (Kawachi et al. al., 2008). In this study, a single irradiation of Nrf2 KO mice with UV-B induces a stronger and longer inflammatory response than for wild-type mice for this gene (Kawachi et al., 2008). Conversely, activation of the Nrf2 protein effectively protects murine cells from ROS damage in vitro and in vivo.

Moreover, the Nrf2 transcription factor is constitutively expressed by the keratinocytes of the skin which is in a normal state, and overexpressed during the healing process (Braun et al., 2002).

Inducers of Nrf2 transcription factor activation have been identified, including sulforaphane, an organosulfuric compound of the isothiocyanate group found in cruciferous plants such as broccoli, Brussels sprouts or cauliflower (Dinkova). -Kostova et al., 2006).

In mouse models, topical application of broccoli extracts, containing sulforaphane, has been shown to exert a protective effect against inflammation (Saw et al., 2011) and photocarcinogenesis (Dinkova-Kostova et al., 2006) UV-B-induced. However, sulphoraphane is a very unstable molecule and, as such, is not suitable for the development of solar products.

There is therefore a clear need to identify new cosmetic active agents that can be formulated in solar products and that can act as inducers of the cells' antioxidant responses, in particular through the activation of the Nrf2 pathway.

Description of the invention

Surprisingly, the Applicant has demonstrated that solar dermocosmetic compositions comprising trimethoxybenzyl acetylsinapate (INCI), a stable compound, meet the need for a composition to ensure endogenous cellular protection vis-à-vis UV radiation . In particular, this active has properties of induction of gene expression controlled by the Nrf2 transcription factor, on which it has an effect comparable to that of the reference asset, sulphoraphane. Such cosmetic or dermatological compositions are therefore of obvious interest in preventing damage caused by UV radiation, advantageously in combination with so-called conventional solar filters.

Note that the use of derivatives of sinapinic acid has already been recommended in the field of cosmetics or pharmacy. In particular, the document WO 2014/108629 describes a long list of 41 derivatives, trimethoxybenzyl acetylsinapate corresponding to compound 5. This is only described for its potentially slimming activity, its anti-aging effect via a compensation of the imbalance of the production of proteins of the skin, and its whitening activity.

The INCI designation trimethoxybenzyl acetylsinapate corresponds to the molecule 3- [4- (acetyloxy) -3,5-dimethoxyphenyl] - (3,4,5-trimethoxyphenyl) methyl ester- (2E) -Propenoic acid (CAS number 1469299-98- 6), characterized by the following structure:

Subsequently, the INCI designation will be used to denominate this molecule.

Trimethoxybenzyl acetylsinapate is known to promote the synthesis of DKK-1 ( Dickkopf-1 ), an intercellular messenger involved in melanogenesis (Yamaguchi et al., 2009). DKK-1 activates the Wnt ( Winnt ) signaling pathway and thus reduces the levels of melanin synthesis in melanocytes. Trimethoxybenzyl acetylsinapate therefore has a depigmenting effect mediated by the activation of DKK-1.

However, to the knowledge of the Applicant, the antioxidant and photoprotective properties of trimethoxybenzyl acetylsinapate, particularly through its activator function of the Nrf-2 pathway illustrated in the present application, have never been reported.

According to a first aspect, the present invention relates to a cosmetic or dermatological composition comprising trimethoxybenzyl acetylsinapate. According to a preferred embodiment in relation to its photoprotective properties, such a composition further comprises at least one sunscreen, advantageously a UV filter.

According to another aspect, the present invention relates to the use of trimethoxybenzyl acetylsinapate in a cosmetic or dermatological composition for its antioxidant and photoprotective activity.

Advantageously, trimethoxybenzyl acetylsinapate represents between 0.001% and 10% by total weight of the composition, preferably between 0.01% and 1%.

Any form of trimethoxybenzyl acetylsinapate may be employed in a composition within the meaning of the invention. Trimethoxybenzyl acetylsinapate can be obtained from plant extracts or microorganisms or by chemical synthesis. Thus, the composition according to the invention may comprise trimethoxybenzyl acetylsinapate of chemical origin or of natural origin, preferably of chemical origin.

In practice, trimethoxybenzyl acetylsinapate can be used in the composition according to the invention in purified or isolated form, with a purity of at least 60%, preferably at least 70%, advantageously at least 80%, and even more advantageously at least equal to 90%, or even at least 95%.

Alternatively, it may be in the form of a mixture with a carrier capable of increasing its solubility and / or its cutaneous bioavailability.

In a particular embodiment, the active ingredient trimethoxybenzyl acetylsinapate is vectorized in a clay support. In practice, the raw material INACLEAR®, marketed by the companies INABATA and PHARMASYNTHESE and corresponding to the INCI designations Bentonite (and) Trimethoxybenzyl acetylsinapate, can be used in the context of the present invention.

As already stated and advantageously, the composition according to the invention further comprises at least one UV filter.

For the purposes of the invention, the term "UV filter" includes organic or inorganic compounds capable of filtering UV-A, UV-B and / or UV-C.

Thus, the addition of UV filters in a composition containing trimethoxybenzyl acetylsinapate makes it possible to improve the protective effect of the skin, superficial body growths, lips, hair and / or mucous membranes, the harmful effects of UV radiation by combining a form of protection external to the internal protection highlighted in the present application.

According to the invention, it may as well be inorganic filters as chemical or organic filters.

The compositions according to the invention may contain one or more broad-spectrum UV filters, that is to say compounds or mixtures which absorb UV-A, UV-B, UV-C and possibly visible light. .

Among the broad-spectrum organic filters, the filters corresponding to the following INCI designations may be used in the context of the invention: tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, methylene bis-benzotriazolyl tetramethylbutylphenol. By way of example, these are marketed by BASF under the names TINOSORB S® / TINOSORB AQUA®, TINOSORB A2B®, TINOSORB M®, respectively. Another example of a broad-spectrum filter adapted to the composition according to the invention corresponds to the INCI designation diethylhexyl butamido triazone, for example marketed by SIGMA 3V under the name UVASORB HEB®.

Thus, and in a particular embodiment, the composition according to the invention comprises at least one filter selected from the following group of compounds identified by their INCI designation: tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, and methylene bis-benzotriazolyl tetramethylbutylphenol, diethylhexyl butamido triazone, or mixtures thereof.

Advantageously, the composition comprises the bis-ethylhexyloxyphenol methoxyphenyl triazine filter.

According to another embodiment, instead of or in addition to the broad-spectrum filter (s), the composition contains at least one UV-A and / or UV-B filter, organic and / or mineral, which can be present in aqueous phase (lipophilic) and / or oily (fat-soluble).

Thus, and by way of example, the composition according to the invention may contain liposoluble UV-B filters capable of contributing to the stabilization or solubilization of the broad-spectrum filters or else of stabilizing each other and thereby increasing the sun protection factor (SPF or SPF ).

Advantageously, such filters correspond to the following INCI designations: homosalate, octocrylene, ethylhexyl salicylate, ethylhexyl triazone.

In a preferred embodiment, the composition according to the invention comprises ethylhexyl triazone, marketed by BASF under the name UVINUL T150®.

In another embodiment, the liposoluble UV-B filter is α- (trimethylsilyl) -ω- (trimethylsilyloxy) poly [oxy (dimethyl) silylene] -co- [oxy (methyl) (2- {4- [ 2,2-bis (ethoxycarbonyl) vinyl] phenoxy} -1-méthylèneéthyl) silylene] -co- [oxy (methyl) (2- (4- [2,2-bis (ethoxycarbonyl) vinyl] phenoxy) prop-1- enyl) silylene], a silicone polymer capable of filtering in UV-B. This filter corresponds for example to the cosmetic raw material Parsol SLX®, sold by the company DSM according to the INCI designation polysilicone-15.

In a preferred embodiment, the composition according to the invention comprises at least one UV-B filter selected from the following group of compounds identified by their INCI designation: homosalate, octocrylene, ethylhexyl salicylate, ethylhexyl triazone, polysilicone-15, or their mixtures.

In a particular embodiment, the composition is free of the following filters: 4-methylbenzylidene camphor, benzophenone-2, benzophenone-3, ethylhexyl methoxycinnamate.

In an advantageous embodiment, the composition according to the invention comprises at least one UV-A filter, in order to ensure complete filtration of the harmful part of the solar spectrum.

Advantageous UV-A filters within the meaning of the present invention are butyl methoxydibenzoylmethane (INCI) and diethylamino hydroxybenzoyl hexylbenzoate (INCI), respectively corresponding to the Parsol 1789® raw materials marketed by DSM and UVINUL® A + marketed by the company. BASF.

In a particular embodiment, the UV-A filter is bis (diethylaminohydroxybenzoyl benzoyl) piperazine (INCI) (CAS No. 919803-06-8), corresponding for example to the C1332® raw material marketed by BASF.

Thus, and in a preferred embodiment, the composition according to the invention comprises at least one filter selected from the following group of compounds identified by their INCI designation: butyl methoxydibenzoylmethane, diethylamino hydroxybenzoyl hexylbenzoate, bis (diethylaminohydroxybenzoyl benzoyl) piperazine, or their mixtures.

• le filtre correspondant à la désignation INCI disodium phenyl dibenzimidazole tetrasulfonate, notamment disponible sous la dénomination Neo Heliopan® AP (Symrise) ;
• le filtre correspondant à la désignation INCI phenylbenzimidazole sulfonic acid, notamment disponible sous la dénomination Neo Heliopan® hydro (Symrise), de préférence en combinaison avec un acide aminé basique, avantageusement de l'arginine. En pratique, l'acide aminé basique représente entre 0,5 et 2% en poids total de la composition, de préférence entre 1 et 1,5%.

Other advantageous UV filters within the meaning of the present invention are water-soluble filters, for example:

• the filter corresponding to the INCI designation disodium phenyl dibenzimidazole tetrasulfonate, especially available under the name Neo Heliopan® AP (Symrise);
• the filter corresponding to the INCI designation phenylbenzimidazole sulfonic acid, especially available under the name Neo Heliopan® hydro (Symrise), preferably in combination with a basic amino acid, preferably arginine. In practice, the basic amino acid represents between 0.5 and 2% by total weight of the composition, preferably between 1 and 1.5%.

In a preferred embodiment, the composition according to the invention comprises at least one water-soluble filter selected from the following group of compounds identified by their INCI designation: Disodium phenyl dibenzimidazole tetrasulphonate, phenylbenzimidazole sulphonic acid, or mixtures thereof.

Advantageously, inorganic mineral filters, or inorganic screens, are metal oxides and / or other compounds that are difficult to dissolve or insoluble in water, in particular the oxides of titanium (TiO ₂ ), zinc (ZnO) and iron (Fe ₂ O ₃ ), zirconium (ZrO ₂ ), silicon (SiO ₂ ), manganese (for example MnO), aluminum (Al2O ₃ ), or cerium (Ce ₂ O ₃ ).

According to one particular embodiment, the inorganic mineral filters can be used in the form of an oily or aqueous predispersion available on the market. These predispersions can advantageously be added dispersion aids and / or solubilization mediators.

The inorganic inorganic filters may also be surface-treated or encapsulated to give them a hydrophilic, amphiphilic or hydrophobic character. This surface treatment can consist in that the mineral filters are provided with a thin inorganic and / or hydrophilic and / or hydrophobic organic film.

In a preferred embodiment, the composition according to the invention comprises at least one mineral screen selected from the following group of compounds identified by their INCI designation: zinc oxide, titanium dioxide, or mixtures thereof.

The lists of UV filters cited that can be implemented within the meaning of the present invention are of course given for information only and not limiting.

Advantageously, the UV filters as described above, present in the composition according to the invention, represent from 0.1% to 30% by total weight of the composition, advantageously from 0.5% to 20%, still more preferably from 1% to 15%, to provide cosmetic compositions that protect the skin or integuments of the entire UV radiation range. According to one particular embodiment, the composition according to the invention has a sun protection factor ("SPF" or SPF) greater than or equal to 10, preferably greater than or equal to 20, advantageously greater than or equal to 30, and even more advantageously greater than or equal to 50.

According to a preferred embodiment, the composition according to the invention comprises a UV-A / UV-B protection ratio equal to or greater than 1/3.

• le butyloctyl salicylate (INCI), photostabilisant représentant avantageusement entre 0,01 % et 10 % en poids total de la composition, encore plus avantageusement ente 0,1 % et 2 %. Cette matière première est par exemple commercialisée par la société HALLSTAR sous le nom de Hallbrite® BHB ;
• le benzotriazolyl dodecyl p-cresol (INCI), photostabilisant représentant avantageusement entre 0,01 % et 10 % en poids total de la composition, encore plus avantageusement entre 0,1 % et 2 %. Cette matière première est par exemple commercialisée par la société BASF sous le nom de TINOGARD® TL ;
• le pongamol (INCI), molécule végétale absorbant dans les UV-A, représentant avantageusement entre 0,5 et 2% en poids total de la composition, encore plus avantageusement de l'ordre de 1%. A titre d'exemple, la matière première Pongamia Extract commercialisée par la société GIVAUDAN peut être utilisée dans le cadre la présente invention ;
• l'ethylhexyl methoxycrylene (INCI), photostabilisant, solubilisant et « booster » de SPF représentant avantageusement entre 1 % et 5 % en poids total de la composition. La matière première SolaStay® SI commercialisée par la société HALLSTAR peut être utilisée dans le cadre de la présente invention ;
• un copolymère de styrène acrylate (INCI : styrene/acrylate copolymer), représentant de préférence entre 1% et 10% en poids total de la composition selon l'invention. Les matières premières SunSpheres® H53 et SunSpheres® PGL Polymer, commercialisées par la société DOW CHEMICALS, peuvent être utilisées dans le cadre de la présente invention ;
• le diethylhexyl syringylidene malonate (INCI), représentant avantageusement entre 1 % et 10 % en poids total de la composition. La matière première OXYNET® ST, commercialisée par la société MERCK, peut être utilisée dans le cadre de la présente invention ;
• un polyester hydrodispersible, correspondant aux désignations INCI polyester-5 (and) Sodium silicoaluminate, représentant avantageusement entre 1 % et 10 % en poids total de la composition, notamment l'EASTMANN AQ™38S Polymer commercialisé par la société SAFIC-ALCAN ;
• un copolymère d'acrylate ayant une température de transition vitreuse de -5 °C à -15 °C telle que mesurée par calorimétrie différentielle à balayage, ledit copolymère représentant avantageusement entre 1 % et 10 % en poids total de la composition. Par exemple, un polymère correspondant à la désignation INCI Acrylate copolymer, tel que la matière première EPITEX 66, commercialisée par la société DOW CHEMICALS, peut être utilisée dans le cadre de la présente invention.

The composition according to the invention, consisting at least of trimethoxybenzyl acetylsinapate, advantageously combined with at least one UV filter, may further comprise a SPF booster, that is to say an enhancer of the sun protection factor, and / or a light stabilizer, ie an ingredient which makes it possible to increase the SPF or to photostabilize the filters, such an ingredient not being itself considered as a sunscreen. We can for example quote:

• butyloctyl salicylate (INCI), the photostabilizer advantageously representing between 0.01% and 10% by total weight of the composition, still more advantageously between 0.1% and 2%. This raw material is for example marketed by HALLSTAR under the name of Hallbrite® BHB;
• benzotriazolyl dodecyl p-cresol (INCI), photostabilizing advantageously representing between 0.01% and 10% by total weight of the composition, still more advantageously between 0.1% and 2%. This raw material is for example marketed by BASF under the name TINOGARD® TL;
• pongamol (INCI), a plant molecule absorbing in the UV-A, advantageously representing between 0.5 and 2% by total weight of the composition, more advantageously of the order of 1%. By way of example, the Pongamia Extract raw material marketed by GIVAUDAN may be used in the context of the present invention;
• ethylhexyl methoxycrylene (INCI), photostabilizing, solubilizing and "booster" SPF preferably representing between 1% and 5% by total weight of the composition. The SolaStay® SI raw material marketed by HALLSTAR may be used in the context of the present invention;
• a styrene acrylate copolymer (INCI: styrene / acrylate copolymer), preferably representing between 1% and 10% by total weight of the composition according to the invention. The SunSpheres® H53 and SunSpheres® PGL Polymer raw materials marketed by DOW CHEMICALS can be used in the context of the present invention;
• diethylhexyl syringylidene malonate (INCI), advantageously representing between 1% and 10% by total weight of the composition. The OXYNET® ST raw material, marketed by MERCK, may be used in the context of the present invention;
• a water-dispersible polyester, corresponding to the INCI polyester-5 (and) Sodium silicoaluminate designations, advantageously representing between 1% and 10% by total weight of the composition, in particular EASTMANN AQ ™ 38S Polymer sold by the company SAFIC-ALCAN;
• an acrylate copolymer having a glass transition temperature of -5 ° C to -15 ° C as measured by differential scanning calorimetry, said copolymer preferably being from 1% to 10% by total weight of the composition. For example, a polymer corresponding to the INCI designation Acrylate copolymer, such as the raw material EPITEX 66, sold by the company Dow Chemicals, can be used in the context of the present invention.

In a particular embodiment, the composition according to the invention also comprises one or more substances capable of filtering visible light, in particular blue light. By way of example, the compounds described in the document EP 1 484 051 can be used to ensure blue light filtration.

According to another embodiment, the composition according to the invention may furthermore comprise an extract of the bacterium Arthrobacter agilis, in particular an extract rich in carotenoids, as described in document WO 2014/167247 . Advantageously, the composition according to the invention comprises from 0.00001% to 0.1% by total weight of the composition, more advantageously from 0.0001% to 0.001% of such a dry extract.

In a preferred embodiment, the composition according to the invention further comprises other components that can contribute to the internal protection by an action that may consist of a protection of the DNA, a decrease of the immunosuppression induced by the radiation. UV, an antiradical action or a combined effect of these actions.

The protective action of a preparation according to the invention against oxidative stress or against the effect of free radicals can be further improved if it further comprises one or more antioxidants, easily selected by man of the art, for example in the following list: totarol, magnolol, honokiol, amino acids and their derivatives, imidazoles (urocanic acid) and their derivatives, peptides (D and / or L-carnosine) and their derivatives (for example, anserine, hypotaurine, taurine), carotenoids, carotenes (a-carotene, β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl esters, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleic, cholesteryl and glycerol) and salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic and its derivatives, sulfoximine compounds (buthionine sulfoximine, homocysteine sulfoximine, buthionine sulfones, penta-, hexa- and heptathionine sulfoximine), chelating agents (such as α-hydroxygras, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (such as citric acid, lactic acid, or malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA , EGTA, pentasodium tetramethylene phosphonate of ethylenediamine and its derivatives, unsaturated fatty acids and their derivatives, vitamin A and its derivatives (vitamin A palmitate), coniferyl benzoate of benzoin resin, acid rutinic acid and its derivatives, α-glycosyl rutin, ferulic acid and its derivatives, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone, quercetin, uric acid and s, mannose and derivatives thereof, zinc and its derivatives (ZnO, ZnSO ₄ ), selenium and its derivatives (selenomethionine), stilbenes and their derivatives (stilbene oxide, trans-oxide -stilbene).

In a particular embodiment, the composition according to the invention additionally contains glycyrrhetinic acid, a derivative or a salt of this acid, used as a soothing agent (anti-inflammatory agent) and representing between 0.01% and 2%. in total weight of the composition, preferably between 0.1% and 1%.

• un agent antiradicalaire préservant les structures cellulaires, tel que par exemple la vitamine E et/ou ses dérivés liposolubles ou hydrosolubles, en particulier le tocotriénol et/ou le tocophérol, représentant avantageusement entre 0,001 et 10 % en poids total de la composition, encore plus avantageusement entre 0,02 et 2 %, de préférence de l'ordre de 0,04 % ;
• un agent limitant l'immunosuppression, tel que par exemple la vitamine PP, représentant avantageusement entre 0,001 et 1 % en poids total de la composition, encore plus avantageusement de 0,01 % à 0,3 %;
• un agent protecteur de la protéine p53, tel que par exemple l'épigallocatéchine gallate (EGCG), représentant avantageusement entre 0,001 et 0,1 % en poids total de la composition, encore plus avantageusement de 0,005 % à 0,05 %.

According to another preferred characteristic of the invention, the cosmetic and / or dermatological composition contains at least one or all of the following constituents exerting an in vivo biological activity on the cells of the skin, lips, hair and / or mucous membranes. subjected to UV-A and / or UV-B radiation, respectively:

• an antiradical agent preserving cell structures, such as, for example, vitamin E and / or its liposoluble or water-soluble derivatives, in particular tocotrienol and / or tocopherol, advantageously representing between 0.001 and 10% by total weight of the composition, and even more preferably between 0.02 and 2%, preferably of the order of 0.04%;
• an agent limiting the immunosuppression, such as, for example, vitamin PP, advantageously representing between 0.001 and 1% by total weight of the composition, still more advantageously from 0.01% to 0.3%;
• a protector of the p53 protein, such as for example epigallocatechin gallate (EGCG), advantageously representing between 0.001 and 0.1% by total weight of the composition, still more advantageously from 0.005% to 0.05%.

The composition according to the invention may also further comprise peptide extracts of soya and / or wheat, such as those described in US Pat. EP 2 059 230 .

In practice, the peptide extracts derived from soybean and wheat seeds are derived from enzymatic hydrolysis of said seeds by means of peptidases which makes it possible to recover peptides with an average size of 700 Daltons. Preferably, the peptide extract of soy is the extract identified under the CAS number 68607-88-5, as well as the peptide extract of wheat is the extract identified under the CAS number 70084-87-6. The wheat and soy extracts can be referred to as INCI Hydrolyzed Wheat Protein and Hydrolyzed Soy Protein, respectively.

In a particular embodiment, the peptide extracts of soya and wheat are used together, for example in a weight ratio respectively between 80/20 and 20/80, advantageously between 70/30 and 30/70, preferably equal to at 60/40.

In an advantageous embodiment, the peptide extracts of soy and / or wheat are free of synthetic tripeptides GHK (glycyl-histidyl-lysine; INCI: Tripeptide-1). In practice, the peptide extracts of soy and / or wheat representing from 0.01% to 20% by total weight of the composition, advantageously from 0.1% to 10%, still more advantageously from 0.2% to 0.7%. .

In an alternative embodiment, the composition according to the invention comprises, in accordance with the teachings of the document FR 2 865 398 the combination of at least one amino acid selected from the group consisting of ectoin, creatine, ergothioneine and / or carnosine, or their physiologically acceptable salts, and mannitol or a derivative of mannitol.

Preferably, the composition according to the invention comprises in a physiologically acceptable medium the amino acid or one of its salts, alone or as a mixture in proportions of between 0.001% and 10% by total weight of the composition, and of preferably between 0.01% and 5%.

The composition according to the present invention preferably comprises, in a physiologically acceptable medium, mannitol or a derivative thereof, in proportions of between 0.01% and 30% by total weight of the composition, advantageously between 0, 1% and 10%.

In a preferred embodiment, the composition according to the invention comprises ectoin and mannitol.

According to a particular embodiment, the composition according to the invention contains one or more other bronzing agents or self-tanning agents. It may be a self-tanner that reacts with the amino acids in the skin in a Maillard reaction or through Michael addition, or a melanogenesis promoter or a propigmenting compound that promotes tanning. natural skin.

Such a substance is preferably present in the composition in an amount ranging from 0.01% to 20% by total weight of the composition, preferably from 0.5% to 15%, even more preferably from 1% to 8%.

The self-tanning substances may be 1,3-dihydroxyacetone (DHA), glycerolaldehyde, hydroxymethylglyoxal, γ-dialdehyde, erythrulose, 6-aldo-D-fructose, ninhydrin, 5-hydroxy-1 , 4-naphthoquinone (juglone), 2-hydroxy-1,4-naphthoquinone (lawsone) or combinations thereof.

The propigmenting substances may be melanocyte stimulating hormone (α-MSH), α-MSH peptide analogs, endothelin-1 receptor agonists, opioid μ agonists, stimulating agents of CAMP, tyrosinase stimulating agents.

In a particular embodiment, the composition according to the invention further comprises, as a self-tanning agent, a combination of dihydroxy methylchromonyl palmitate and a lipophilic form of tyrosine.

As described in the document FR 3 031 301 this combination of active ingredients can effectively stimulate tanning. The dihydroxy methylchromonyl palmitate (CAS number: 1387636-35-2) corresponds, for example, to the cosmetic ingredient marketed by Merck under the name RonaCare® Bronzyl. It is in the form of a white powder, odorless, with a purity greater than 99%.

According to a particular embodiment, the dihydroxy methylchromonyl palmitate is present in the composition according to the invention in a proportion of from 0.01% to 10% by total weight of the composition, advantageously from 0.05% to 10%, even more advantageously from 0.1% to 5%, more preferably from 0.1% to 0.5%.

The lipophilic form of tyrosine, within the meaning of the invention, is an ingredient based on tyrosine and having a more pronounced lipophilic character than tyrosine. The lipophilic form of tyrosine may especially correspond to oleoyl tyrosine (CAS number: 147732-57-8), which is found, for example, in the liquid cosmetic ingredient TYR-OL, marketed by SEDERMA, and which comprises about 50% by weight of oleoyl tyrosine in butylene glycol (about 30% + about 20% oleic acid), or in the liquid cosmetic ingredient TYR-EXCEL, sold by SEDERMA, which comprises about 50% by weight of oleoyl tyrosine, about 20% oleic acid (CAS No. 112-80-1) and about 30% of Luffa cylindrica oil (sponge pumpkin seed oil; CAS No. 1242417-48- 6).

According to another embodiment, the lipophilic form of tyrosine corresponds to a vegetable oil in which tyrosine has been formulated.

According to a particular embodiment, the vegetable oil is oleic sunflower oil, advantageously deodorized. Thus, the OLEOACTIF TYROSINE BASE HELIANTHUS ANNUS raw material marketed by the OLEOS company, and corresponding to the INCI designations Helianthus annuus seed oil (and) tyrosine (and) glyceryl stearate, may be used in the context of the present invention.

In practice, the lipophilic form of tyrosine, such as in cosmetic ingredients based on oleoyl-tyrosine (advantageously 50% by weight) or on tyrosine formulated in vegetable oil, represents between 0.1% and 10% by total weight of the composition, advantageously between 1 and 3%, even more advantageously between 1% and 1.5%.

• de l'azéilate de lysine, ou d'autres dérivés ou sels de l'acide azélaïque ;
• de l'andrographolide, notamment l'extrait d'Andrographis paniculata correspondant à la désignation INCI Andrographis paniculata leaf extract ;
• de l'acide ascorbique natif (vitamine C) ou ses dérivés, notamment les dérivés correspondant aux INCI Ascorbyl Glucoside Ethyl ascorbic acid, Ascorbyl methylsilanol pectinate, Sodium ascorbyl phosphate et Ascorbyl tetraisopalmitate ;
• de l'arbutine ou un extrait végétal la contenant, notamment l'extrait de busserole correspondant à la désignation INCI Arctostaphylos uva-ursi leaf extract ;
• de la glabridine ou un extrait végétal la contenant, notamment les extraits de réglisse correspondant à la désignation INCI Glycyrrhiza glabra root extract, Glycyrrhiza inflata root extract, Glycyrrhiza uralensis root extract ;
• les peptides biomimétiques correspondant aux désignations INCI hexapeptide 2 et/ou nonapeptide-1 ;
• un extrait aqueux d'une algue dénommée Palmaria palmata, notamment l'extrait correspondant à la désignation INCI Palmaria palmata extract ;
• le 4-n-butylresorcinol ;
• de la vitamine PP, également appelée niacinamide ou nicotinamide, et ses dérivés ;

ou leurs mélanges.The composition according to the invention may also contain active agents having depigmenting properties, for example:

• lysine azeilate, or other derivatives or salts of azelaic acid;
• andrographolide, in particular the Andrographis paniculata extract corresponding to the INCI designation Andrographis paniculata leaf extract;
• native ascorbic acid (vitamin C) or its derivatives, especially the derivatives corresponding to INCI Ascorbyl Glucoside Ethyl ascorbic acid, Ascorbyl methylsilanol pectinate, Sodium ascorbyl phosphate and Ascorbyl tetraisopalmitate;
• arbutin or a plant extract containing it, in particular the bearberry extract corresponding to the INCI designation Arctostaphylos uva-ursi leaf extract;
• glabridine or a plant extract containing it, in particular the liquorice extracts corresponding to the INCI designation Glycyrrhiza glabra root extract, Glycyrrhiza inflata root extract, Glycyrrhiza uralensis root extract;
• biomimetic peptides corresponding to the INCI hexapeptide 2 and / or nonapeptide-1 designations;
• an aqueous extract of an alga called Palmaria palmata, in particular the extract corresponding to the INCI designation Palmaria palmata extract;
• 4-n-butylresorcinol;
• vitamin PP, also known as niacinamide or nicotinamide, and its derivatives;

or their mixtures.

The composition according to the invention may also contain active agents having healing properties, for example an antimicrobial agent chosen from the active ingredients corresponding to the following INCI designations: Copper sulfate, zinc sulfate, sodium hyaluronate, Vitis vinifera (grape) vine extract, or their mixtures.

The composition according to the invention may also contain active agents having sebocorrectice, keratolytic, seboregulatory properties and / or anacneic activity, in order to allow the formulation of acne-treating sun products.

For example, the composition according to the invention may comprise an antimicrobial agent chosen from the active ingredients corresponding to the INCI names: propyl gallate, dodecyl gallate, Ginkgo biloba leaf extract, bakuchiol, dihydromyricetine, zinc gluconate, salicylic acid, or mixtures thereof.

• un agent amplificateur du facteur de protection solaire ou booster SPF ;
• un photostabilisant ;
• un extrait de la bactérie Arthrobacter agilis, avantageusement riche en caroténoïdes ;
• un méroterpène, avantageusement du bakuchiol ;
• au moins un polyol choisi parmi le xylitol, le rhamnose, le sorbitol et le mannitol ;
• un extrait de Gingko biloba ;
• du butyl hydroxytoluène (BHT) ;
• un extrait de la plante Andrographis paniculata ;
• un extrait de l'algue Palmaria palmata ;
• un extrait des algues Laminaria ochroleuca, Blidingia Minima ou Laminaria Saccharina ;
• un extrait de la plante Zanthoxylum alatum ;
• du panthénol ;
• un agent antiradicalaire préservant les structures cellulaires, tel que par exemple la vitamine E et/ou un de ses dérivés liposoluble ou hydrosoluble, en particulier le tocotriénol et/ou le tocophérol ;
• de l'acide salicylique ou un de ses dérivés ;
• un extrait de bois de cade ;
• un extrait de Boldo ;
• un extrait de Reine des prés ;
• de l'acide glycyrrhétinique ou un de ses dérivés, ou un de leurs sels ;
• un agent limitant l'immunosuppression, avantageusement la vitamine PP ;
• un agent protecteur de la protéine p53, avantageusement l'épigallocathéchine gallate (EGCG) ;
• un extrait d'huile de karanja issue du Pongamia glabra ;
• des paraffines linéaires ;
• de l'ATP (adénosine-5 tri-phosphate) ou un précurseur d'ATP, par exemple la Gp₄G (diguanosine tétraphosphate), ou l'Ap₄A (diadénosine tétraphosphate) ;
• un agent limitant l'action des ions fer impliqués dans la formation des radicaux libres, avantageusement l'EDTA ;
• un extrait peptidique de soja et/ou de blé ;
• un acide aminé ou dérivé d'acide aminé choisi parmi le groupe constitué de l'ectoïne, la créatine, l'ergothionéine, la carnosine, la tyrosine, la décarboxycarnosine, la glutamine et leurs sels ;
• un agent bronzant ou autobronzant ;
• un agent dépigmentant ;
• un agent cicatrisant ;
• un agent sébocorrecteur, kératolytique, séborégulateur et/ou antiacnéique.

The composition according to the invention may therefore also comprise at least one ingredient chosen from the following list:

• an enhancer agent of the sun protection factor or SPF booster;
• a light stabilizer;
• an extract of the bacterium Arthrobacter agilis, advantageously rich in carotenoids;
• a meroterpene, advantageously bakuchiol;
• at least one polyol selected from xylitol, rhamnose, sorbitol and mannitol;
• an extract of Gingko biloba;
• butylated hydroxytoluene (BHT);
• an extract of the plant Andrographis paniculata;
• an extract of the alga Palmaria palmata;
• an extract of the seaweed Laminaria ochroleuca, Blidingia Minima or Laminaria Saccharina;
• an extract of the plant Zanthoxylum alatum;
• panthenol;
• an antiradical agent preserving cell structures, such as, for example, vitamin E and / or one of its liposoluble or water-soluble derivatives, in particular tocotrienol and / or tocopherol;
• salicylic acid or a derivative thereof;
• an extract of cade wood;
• an extract of Boldo;
• an extract of Meadowsweet;
• glycyrrhetinic acid or a derivative thereof, or a salt thereof;
• an agent limiting the immunosuppression, advantageously vitamin PP;
• a protector of the p53 protein, advantageously epigallocathechin gallate (EGCG);
• an extract of karanja oil from Pongamia glabra;
• linear paraffins;
• ATP (adenosine-5-triphosphate) or a precursor of ATP, for example Gp ₄ G (diguanosine tetraphosphate), or Ap ₄ A (diadenosine tetraphosphate);
• an agent limiting the action of iron ions involved in the formation of free radicals, advantageously EDTA;
• a peptide extract of soy and / or wheat;
• an amino acid or amino acid derivative selected from the group consisting of ectoin, creatine, ergothioneine, carnosine, tyrosine, decarboxycarnosine, glutamine and their salts;
• a tanning or self-tanning agent;
• a depigmenting agent;
• a healing agent;
• a sebocorrector, keratolytic, seboregulatory and / or antiacne agent.

The composition according to the invention may also contain adjuvants such as those conventionally used in the field of cosmetics, such as active agents, preservatives, antioxidants, complexing agents, solvents, fragrances, fillers, bactericides, electrolytes, odor absorbers, dyes or lipid vesicles. The choice of these adjuvants, as well as their concentrations, must be determined in such a way that they do not modify the properties and advantages sought for the composition of the present invention.

The composition of the invention is intended for topical application and more particularly for application to the skin, lips, hair and / or mucous membranes. Thus and in the context of the invention, such a composition is in particular intended for the protection of the skin and / or integuments, in particular the mucous membranes, the lips and the hair, against UV radiation.

The composition of the invention may be in any galenical form normally used in the cosmetic and dermatological fields, such as, but not limited to, in the form of an optionally gelled aqueous solution, a dispersion of the type lotion, an emulsion Oil in Water (O / W) Water in Oil (W / H), more or less fluid, or a multiple emulsion such as for example a triple emulsion (W / O / W or O / W) / H), or in the form of a vesicular dispersion of ionic type (liposomes) and / or nonionic, a two-phase composition devoid of emulsifiers and gelling agents whose immiscible phases are separated during storage, foam, stick, anhydrous oil, spray or mist.

In a preferred embodiment, the composition according to the invention is an W / O emulsion. Advantageously, the W / O emulsions according to the invention comprise PEG-30 dipolyhydroxystearate (INCI) as an emulsifier.

Preferably, the W / O emulsions according to the invention comprise a solubilizer chosen from the following group of compounds identified by their INCI designation: dicaprylyl carbonate, C12-15 alkyl benzoate, dibutyl adipate, alone or as a mixture. These emulsifiers and solubilizers are available on the market from several suppliers.

In an alternative embodiment, the composition according to the invention is an O / W emulsion. Advantageously, the O / W emulsions according to the invention comprise an emulsifier selected from the following group of compounds identified by their INCI designation: potassium cetyl phosphate, glyceryl stearate, PEG-100 stearate and C20-22 alkyl phosphate / C20-C22 alkyl alcohol , tribehenin PEG-20 Esters and their mixtures.

Preferably, the O / W emulsions according to the invention comprise a solubilizer chosen from the following group of compounds identified by their INCI designation: dicaprylyl carbonate C12-15 alkyl benzoate, dibutyl adipate, disopropyl sebacate alone or their mixtures. These emulsifiers and solubilizers are available on the market from several suppliers.

The composition according to the invention may also comprise preservatives. Any preservative suitable for use in cosmetic or dermatological compositions can be used in the formulation of a composition according to the invention.

Advantageously, the preservatives used are alkanediols, even more advantageously 1,2-alkanediols or 1,3-alkanediols, and mixtures thereof.

In a preferred embodiment, the preservative is a 1,2-diol selected from 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol and 1,2-hexanediol. -decanediol, or mixtures thereof.

In an alternative embodiment, the preservative is a 1,3-diol selected from 1,3-propanediol and 1,3-butanediol, or mixtures thereof. In practice, these alkanediols are marketed by several companies, including SYMRISE or MINACARE.

Preferably, the composition according to the invention comprises between 0.01% and 2% by total weight of the diol composition, advantageously between 0.1% and 1%, for example 0.5%.

Another contribution of the invention relates to the demonstration of the antioxidant activity of a composition comprising trimethoxybenzyl acetylsinapate, via the activation of Nrf2. As described in the literature, this antioxidant activity is correlated with an anti-radical activity and a protective effect vis-à-vis the UV radiation.

• agent antioxydant ;
• agent anti-radicalaire ;
• agent de protection contre la pollution ;
• agent de protection contre les rayonnements UV.

According to another aspect, the present invention therefore relates to a composition comprising trimethoxybenzyl acetylsinapate, advantageously as described above especially in combination with a UV filter, for its use as:

• antioxidant agent;
• anti-radical agent;
• pollution protection officer;
• protective agent against UV radiation.

As a result, such a composition can be used in the prevention and / or treatment of skin, lip, hair, and / or mucosal cell damage caused by solar radiation, in particular UV radiation. As such it allows to fight against aging, especially photoaging.

The manner in which the invention can be realized and the advantages which result therefrom will emerge more clearly from the following exemplary embodiments, given by way of non-limiting indication, in support of the appended figure.

Figure 1 : Effect of trimethoxybenzyl acetylsinapate on the induction of the Nrf2 pathway in the cellular model "ARE Reporter-HepG2". The percentage activation of Nrf2 in the treated cells (HepG2 line) after 18 hours of contact with the trimethoxybenzyl acetylsinapate molecule is indicated.

Examples of realization

The percentages given are given by weight of product relative to the total weight of the composition in the tables below.

Example I - SPF50 + Solar Mist

INCI name % Alcohol denat. 35,00 Bis-ethylhexyloxyphenol methoxyphenyl triazine 10.00 Dibutyl adipate 10.00 Diethylamino hydroxybenzoyl hexyl benzoate 10.00 homosalate 10.00 Diisopropyl sebacate 5.00 Ethylhexyl salicylate 5.00 Ethylhexyl triazone 5.00 Dicaprylyl carbonate 4.9985 Dicaprylyl ether 3.09904 Aqua / Water / Water 1.50 Fragrance (fragrance) 0.30 Trimethoxybenzyl acetylsinapate 0.10 tocopherol 0.002460

Example II - O / W Cream SPF30 +

INCI name % Aqua / Water / Water 64.658 Octocrylene 7.05 C12-15 alkyl benzoate 5.00 Methylene bis-benzotriazolyl tetramethylbutylphenol [nano] 5.00 Dicaprylyl carbonate 4.9985 Ethylhexyl methoxycinnamate 2.9979 Glycerin 2.00 Cetearyl alcohol 1.30 Isononyl isononanoate 1.00 phenoxyethanol 1.00 Microcrystalline cellulose 0.88 Decyl glucoside 0.75 Coco-glucoside 0.70 Hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer 0.592 C20-22 alkyl phosphate 0.55 C20-22 alcohols 0.45 squalane 0,408 Disodium EDTA 0.20 Trimethoxybenzyl acetylsinapate 0.15 Cellulose gum 0.12 Polysorbate 60 0.088 Propylene glycol 0.04 Sorbitan isostearate 0,024 Citric acid 0.02 Xanthan gum 0.02 BHT 0.0021 tocopherol 0.0015

Example III - W / O Cream SPF50 +

INCI name % Aqua / Water / Water 45.057 C12-15 alkyl benzoate 24,90 Bis-ethylhexyloxyphenol methoxyphenyl triazine 5.00 Butyl methoxydibenzoylmethane 5.00 Octocrylene 5.00 Ethylhexyl methoxycinnamate 4.9965 PEG-30 dipolyhydroxystearate 3.00 Glycerin 2.00 Dicaprylyl carbonate 1.7392 Tris-biphenyl triazine 1.50 phenoxyethanol 1.00 Decyl glucoside 0,225 Disodium EDTA 0.20 Stearalkonium hectorite 0.20 Propylene carbonate 0,060 Trimethoxybenzyl acetylsinapate 0.10 Propylene glycol 0.012 Xanthan gum 0.006 BHT 0.0035 tocopherol 0.0008

Example IV - Evaluation of the induction of the Nrf2 pathway by the active agent according to the invention

The aim of the study is to evaluate the induction of the Nrf2 pathway in the cellular model "ARE Reporter-HepG2" (HepG2, BPS BIOSCIENCE) [Lee et al., (2004), Dinkova-Kostova et al. (2002)] by the asset referred to in the invention.

IV.1 EXPERIMENTAL PROTOCOL IV.1.1-Thawing and amplification of "ARE Reporter-HepG2" cells

Thawing of the transfected HepG2 cells was performed according to the recommendations of the cell provider (BPS Bioscience).

The cells of an ampoule were thawed rapidly in a water bath at 37 ° C, then transferred to a tube containing 10 ml of MEM medium (Minimum Essential Medium) supplemented with 10% FCS (Fetal Calf Serum), 1 Penicillin / Streptomycin%, 1 mM sodium pyruvate, 1% non-essential amino acids (= M1 medium). After centrifugation for 5 minutes at 200 g, the cells of the pellet are suspended in 7 ml of preheated culture medium and introduced into a culture flask T25 cm ² for growth.

Before confluence, the cells are detached from the support by incubation with the trypsin / EDTA reagent (ethylene diamine tetraacetic acid) and then centrifuged for 5 minutes at 200 g. The cells of the pellet are suspended in 5 ml of M1 culture medium containing geneticin 600 μg / ml (= medium M2), then they are seeded in culture flasks T75 cm ² for amplification (15 ml of medium M2 ).

All the culture steps (amplification and incubation) were carried out at 37 ° C. under 5% CO ₂ .

IV.1.2- Preparation of the asset to be tested

The test solution was prepared on the day of the activation test. The dilution was carried out in M1 medium. Active Reference / Lot number Mother solution Doses tested Trimethoxybenzyl Acetylsinapate INABATA LB 189/696 1.25% in DMSO 0.00063% 0.00125%

IV.1.3-Preparation of the reference product

A stock solution of sulforaphane (10 mM) (Sigma-Aldrich reference S4441 - lot SLBR6147V) reference activator was prepared in DMSO and then diluted in M1 medium (final concentration 3 μM).

IV.1.4- Detection of the potential cytotoxicity of the test molecule IV.1.4.1. Seeding of the cells

The HepG2 cells were seeded, in M1 medium, in wells of 96-well plates, at a rate of 40,000 cells / well (volume of 100 μl). Only the 60 central wells of the plates were used, the remaining wells received only PBS.

IV.1.4.2. Cell treatment

After adhesion of the cells, the culture medium was removed. The cells were treated with the test products diluted in the M1 culture medium for 18 hours (final volume: 50 μL). On each plate, "control cell" wells were treated with the M1 medium containing the same percentage of DMSO solvent as the wells treated with the test molecules.

After 18 hours of incubation, the media were removed. The cells were rinsed once with 100 μl of PBS and then treated with 100 μl of PBS containing 0.5 mg / ml of MTT (2- (4,5-dimethylthiazol-2-yl) -2,5-bromide. diphenyl tetrazolium).

After 2:30 incubation at 37 ° C under 5% CO ₂ , the MTT was removed and the cells were lysed by adding 100μL of DMSO.

IV.1.4.3. Evaluation of cytotoxicity

The optical density of formazan blue (MTT reduced by mitochondrial dehydrogenases) was measured spectrophotometrically at 540 nm. This optical density is directly proportional to the number of metabolically active cells.

IV. 1.4.4. Data processing

The results were expressed as a percentage of the optical density of the treated wells versus the mean optical density of the "control cell" group treated with the same percentage of the same solvent.

Averages and standard deviations were calculated.

IV. 1.5- Evaluation of the activation of Nrf2 IV.1.5.1. Seeding of the cells

In parallel with the cytotoxicity test, HepG2 cells were also seeded in wells of 96-well plates (opaque plates with transparent background) at the rate of 40,000 cells / well (volume of 100 μL), in M1 medium.

Only the 60 central wells of the plates were used, the remaining wells received only PBS.

IV.1.5.2. Cell treatment

After adhesion of the cells, the M1 culture medium was removed. The cells were treated (final volume: 50 μl) with the test product, diluted in M1 culture medium (n = 3 / concentration to be tested, 1 concentration / product), for 18 hours.

On each plate, "cell-free" wells and "solvent control cell" wells were treated with M1 medium containing 0.5% DMSO.

The "cell-free" wells were used to detect the luminescence related to the background noise of the medium. The "control cell" wells were used to detect the intrinsic luminescence of the test system (without activation).

Sulforaphane at 3 μM has been tested as a reference activator.

IV.1.5.3. Effects evaluation

At the end of the incubation period (18 hours at 37 ° C., 5% CO ₂ ), the cells were lysed by adding 100 μL of the reagent " One-step luciferase assay system ". The luminescence emitted by the neo-synthesized luciferase was evaluated with an Optima luminometer.

IV.1.5.4. Data processing

• Soustraction de la valeur moyenne de la luminescence des puits « sans cellules » à toutes les valeurs de luminescence obtenues dans les puits non traités (« cellules témoins ») et traités.
• Moyenne de la luminescence des puits « cellules témoins »
• Le pourcentage d'induction de la luciférase (proportionnel au niveau d'activation de Nrf2 par les molécules testées) a été calculé selon la formule : $$\frac{100\times \left(\mathrm{Luminescence\; des\; puits\; traités\; avec\; les\; molécules}\right)}{\mathrm{Moyenne\; de\; la\; luminescence\; des\; «cellules\; témoins\; solvant»}}$$
  

The data processing was carried out according to the following protocol:

• Subtraction of mean luminescence value from "cell-free" wells to all luminescence values obtained in untreated ("control") and treated wells.
• Mean luminescence of "control cell" wells
• The percentage of induction of luciferase (proportional to the level of activation of Nrf2 by the tested molecules) was calculated according to the formula: $$\frac{100\times \left(\mathrm{Luminescence\; of\; wells\; treated\; with\; molecules}\right)}{\mathrm{Mean\; luminescence\; of\; "solvent\; control\; cells"}}$$
  

Mean and standard deviations of activation percentages were calculated.

IV.2. RESULTS AND CONCLUSIONS

None of the doses selected from the composition according to the invention induces a significant cytotoxicity in the cellular model studied.

Sulforaphane, tested at 3 μM, increases the luminescence emitted by the treated HepG2 cells, in comparison with the luminescence emitted by the cells treated with the corresponding solvent control, up to 438%. This increase validates the test.

The trimethoxybenzyl acetylsinapate active has a dose-dependent Nrf2 activation rate, with an activation rate of 164% at a dose of 0.00125% relative to the corresponding solvent control ( figure 1 ).

BIBLIOGRAPHY

• Braun S., Hanselmann C., Gassmann MG, Auf dem Keller U., Born-Berclaz C., Chan K., Kan YW, Werner S. (2002) Nrf2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and inflammation in the skin wound healing. Mol Cell Biol. 22 (15): 5492-5505 .
• Copple IM, Goldring CE, Kitteringham NR, BK Park (2008) The Nrf2-Keap1 defense pathway: role in protection against drug-induced toxicity. Toxicology. 246 (1): 24-33 .
• Danovaro R., Bongiorni L., Corinaldesi C., Giovannelli D., Damiani E., Astolfi P., Greci L. Pusceddu A. (2008) Sunscreens cause coral bleaching by viral infections. About Health Perspect 116 (4): 441-447 .
• Dinkova-Kostova, AT. Holtzclaw WD, Cole, RN, Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., Talalay. P. (2002). Direct evidence that sulfhydryl groups of enzymes are regulating the induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci US A. 99 (18): 11908-11913 .
• Dinkova-Kostova AT, Jenkins SN, Fahey JW, Ye L., Wehage SL, Liby KT, Stephenson KK Wade KL, Talalay P. (2006) Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts. Cancer Lett. 240 (2): 243-252 .
• Gorrini C., Baniasadi PS, Harris IS, Silvester J., Inoue S., Snow B., Joshi PA, Wakeham A., Molyneux SD, Martin B., Bouwman P., Cescon DW, Elia AJ, Winterton-Perks Z Cruickshank J., Brenner D., Tseng A., Musgrave M., Berman HK, Khokha R., Jonkers J., Mak TW, Gauthier ML (2013) BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival. J Exp Med. 210 (8): 1529-1544 .
• Kawachi Y., Xu X., Taguchi S., Sakurai H., Nakamura Y., Ishii Y., Fujisawa Y., Furuta J., Takahashi T., Itoh K., Yamamoto M., Yamazaki F., Otsuka F. (2008) Attenuation of UVB-induced sunburn reaction and oxidative DNA damage with no alterations in UVB-induced skin carcinogenesis in Nrf2 gene-deficient mice. J Invest Dermatol. 128 (7): 1773-1779 .
• Lee, JM and. Johnson JA (2004) An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol. 37 (2): 139-143 .
• Lloyd, SA (1993) Stratospheric ozone depletion. Lancet. 342 (8880): 1156-8 .
• Saw CL, Huang MT, Liu Y., Khor TO, Conney AH, Kong AN (2011) Impact of Nrf2 on UVB-induced skin inflammation / photoprotection and photoprotective effect of sulforaphane. Mol Carcinog. 2011 50 (6): 479-486 .
• Yamaguchi Y., Passeron T., Hoashi T., Watabe H., Rouzaud F., Yasumoto K., Hara T., Tohyama C., Katayama I., Miki T., Hearing VJDicckopf 1 (2009) DKK1 regulates skin pigmentation and thickness by affecting Wnt / beta-catenin signaling in keratinocytes. FASEB J. (22) 1009-1020 .

Claims (11)

Composition comprising trimethoxybenzyl acetylsinapate and at least one UV filter. Composition according to Claim 1, characterized in that the trimethoxybenzyl acetylsinapate represents between 0.001% and 10% by total weight of the composition, advantageously between 0.01% and 1%. Composition according to one of the preceding claims, characterized in that the filter is chosen from the following group: tris biphenyl triazine, bisethylhexyloxyphenol methoxyphenyl triazine, methylene bis-benzotriazolyl tetramethylbutylphenol, diethylhexylbutamido triazone and mixtures thereof, advantageously bisethylhexyloxyphenol methoxyphenyl triazine . Composition according to one of the preceding claims, characterized in that the UV filter represents from 0.1% to 30% by total weight of the composition, advantageously from 0.5% to 20%, even more advantageously from 1% to 15% by weight. %. Composition according to one of the preceding claims, characterized in that it further comprises an ingredient chosen from the following group: an enhancer agent for the sun protection factor; a light stabilizing agent; an agent capable of filtering visible light, in particular blue light; an extract of the bacterium Arthrobacter agilis, advantageously rich in carotenoids; at least one polyol chosen from xylitol, rhamnose, sorbitol and mannitol; - an extract of the seaweed Laminaria ochroleuca, Blidingia minima or Laminaria saccharina; an extract of the plant Zanthoxylum alatum; - panthenol; vitamin E or a hydrophilic or lipophilic derivative thereof, or a salt thereof, advantageously tocotrienol or tocopherol; salicylic acid or a derivative thereof; - an extract of cade wood; - an extract of Boldo; - an extract of Meadowsweet; glycyrrhetinic acid or one of its derivatives or salts; an agent limiting the immunosuppression, advantageously vitamin PP, a protector of the p53 protein, advantageously the epigallocathechin gallate (EGCG); - an extract of karanja oil from Pongamia glabra; linear paraffins; ATP (adenosine-5-triphosphate) or a precursor of ATP, for example Gp ₄ G (diguanosine tetraphosphate), or Ap ₄ A (diadenosine tetraphosphate); an agent limiting the action of iron ions involved in the formation of free radicals, advantageously EDTA; a peptide extract of soya and / or wheat; an amino acid or amino acid derivative selected from the group consisting of ectoin, creatine, ergothioneine, carnosine, tyrosine, decarboxycarnosine, glutamine and their salts; - a tanning or self-tanning agent; - a depigmenting agent; a healing agent; a sebocorrector, keratolytic, seboregulatory and / or antiacne agent. Composition according to one of the preceding claims, characterized in that it comprises mannitol and ectoin. Composition according to one of the preceding claims, characterized in that it is in the form of a cream, a lotion, a solution, an emulsion, a gel, an oil, stick, foam, spray or mist. A composition comprising trimethoxybenzyl acetylsinapate for use as an antioxidant. A composition comprising trimethoxybenzyl acetylsinapate for use in the treatment of skin, lip, hair, and / or mucosal cell damage caused by solar radiation, particularly UV radiation. Composition for its use according to Claim 8 or 9, characterized in that the composition is as defined in Claims 1 to 7. Composition for its use according to one of Claims 8 to 10, characterized in that the composition is applied to the skin, the lips, the hair, and / or the mucous membranes.

Images